Unique Bird Sheds Light on Sex Differences in the Brain

COURTESY OF THE PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES
In the womb, sex hormones begin to tell a developing fetus whether to grow up male or female. For the past several decades, scientists have believed that sexual organs, which control these hormones, are solely responsible for the resulting differences between male and female brains. Now the study of an unusual songbird's brain promises to challenge that idea. Scientists have discovered that the half-female and half-male animal's gray matter developed two genetically distinct halves, providing striking evidence that the sex chromosomes within individual cells might play an important role in the development of gender-specific differences in the brain.

A team of scientists led by Arthur Arnold of the University of California at Los Angeles studied a zebra finch that was a gynandromorph, the equivalent of a hermaphrodite in humans. From the right the bird appeared to be male, displaying distinctly male red feathers around the eye and the black-and-white striping that earned the zebra finch its name. The plumage on the flipside, meanwhile, was distinctly female. The bird had both male and female gonads, yet acted male and sang the courtship song that only males sing. If gonadal hormones alone control sex-specific brain function, the two halves of the bird's brain that controls song (known as the song circuit) would be uniformly masculine or feminine. To determine whether this was the case, the team examined slices of the deceased animal's brain with an RNA probe able to detect the presence of sex chromosomes within individual brain cells. (In birds, the sex chromosomes are known as W and Z. Normal males have two Z chromosomes and females have one W and one Z chromosome.)

The scientists found that the right half of the brain contained almost no W chromosomes, whereas the left half was full of them, indicating genetically male and female halves of the brain. "It blew me away," Arnold says. The two sides of the brain were exposed to the same mix of hormones during development, yet the song circuit was much larger on the male side of the creature's brain than on the female side. The findings, published online this week by the Proceedings of the National Academy of Sciences, provide the strongest evidence to date in support of the notion that sex chromosomes acting on single cells play a role in differences between male and female brains. These results might help determine whether the genetic sex of a cell influences its susceptibility to disease, Arnold explains. Certain conditions affect one sex more than the other, he notes, so "if the genetics of a cell affects the progress of a disease, it might suggest specific causes or treatments for disease."